Methamphetamine hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the trade name "Desoxyn".[2] However, it is rarely prescribed due to its abuse potential, typically being reserved for cases of severe obesity or ADHD in which all other treatment options have been exhausted.

Unlike amphetamine at therapeutic doses, methamphetamine at moderate to heavy recreational doses is considered to be directly neurotoxic to humans, damaging both dopamine and serotoninneurons within the central nervous system that are essential in maintaining the proper processing and integration of sensory information, its integration and controlling motor and behavioral output.[citation needed] Additionally, there is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity.[citation needed]

Due to its potent psychostimulant effects, established toxicity profile, and ability to cause mental and physical dependence and addiction when misused, it is highly advised to use harm reduction practices if choosing to consume this substance.

Pure "shards" of Methamphetamine Hydrochloride, commonly known as "Crystal Meth".

History and culture

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Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine.[3] Shortly after, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi.[4] Neither drug had a pharmacological use until 1934, when Smith, Kline and French began selling amphetamine as an inhaler under the trade name Benzedrine as a decongestant.[5]

During World War II, amphetamine and methamphetamine were used extensively by both the Allied and Axis forces for their stimulant and performance-enhancing effects.[6][7] Eventually, as the addictive properties of the drugs became known, governments began to place strict controls on the sale of the drugs.[8] For example, during the early 1970s in the United States, amphetamine became a schedule II controlled substance under the Controlled Substances Act.[9]

Despite strict government controls, both amphetamine and methamphetamine have still been used legally or illicitly by individuals from a variety of backgrounds for different purposes.[10][11][12][13]

Due to the large underground market for these drugs, they are frequently illegally synthesized by clandestine chemists, trafficked, and sold on the black market.[14] Based upon drug and drug precursor seizures, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine.[citation needed]

Chemistry

Methamphetamine, or N-methylamphetamine, is a synthetic molecule of the amphetamine family. Molecules of the amphetamine class contain a phenethylamine core featuring a phenyl ring bound to an amino (NH2) group through an ethyl chain with an additional methyl substitution at Rα. Amphetamines are alpha-methylated phenethylamines. Methamphetamine contains an additional methyl substitution at RN, a substitution which is shared with MDMA, methcathinone, and mephedrone.

Stereoisomers

Methamphetamine exists as two enantiomers: dextrorotary and levorotary. Dextrorotatory or dextromethamphetamine (also known as d-methamphetamine) is a stronger central nervous system (CNS) stimulant than levomethamphetamine; however, both are considered to be dependence-forming and addictive when misused and capable of producing similar toxicity symptoms at heavy recreational doses.[citation needed]

Pharmacology

Methamphetamine primarily affects the central nervous system (CNS) by acting as a releasing agent for neurotransmitters such as dopamine, norepinephrine, and serotonin. It also acts as a reuptake inhibitor, increasing levels of monoamines by forcing the neurotransmitters out of their storage vesicles and expelling them into the synaptic gap by making the dopamine transporters work in reverse.[15] Other mechanisms by which methamphetamine are known to increase monoamine levels are by:

Decreasing the expression of dopamine transporters at the cell surface, which has the same effect as listed above.

Increasing cytosolic levels of monoamines by inhibiting the activity of monoamine oxidase (MAO)

Increasing the activity and expression of the dopamine-synthesizing enzyme tyrosine hydroxylase (TH)

In addition to releasing potent amounts of monoamines, MA has a high lipid solubility which leads to a relatively fast transfer of the drug across the blood-brain barrier and a quick onset in comparison to other stimulants.[16] All of this results in feelings of reward, euphoria, and stimulation as well as an unpleasant offset.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWikicontributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects

Stimulation - In terms of its effects on the physical energy levels of the user, methamphetamine is usually considered to be extremely energetic and stimulating in a fashion that is identical to that of amphetamine, but stronger than that of modafinil, caffeine, and MDMA. It is similar yet distinct from the stimulation experienced on MDMA, encouraging physical activities such as dancing, socializing, running, or cleaning. The particular style of stimulation which methamphetamine presents can be described as forced. This means that at higher dosages, it becomes difficult or impossible to keep still as jaw clenching, involuntarily bodily shakes and vibrations become present, resulting in extreme shaking of the entire body, unsteadiness of the hands, and a general lack of motor control.

Physical euphoria - As a potent stimulant, methamphetamine is capable producing states of intense physical euphoria, especially when it is vaporized or injected. However, the initial rush of euphoria can wear off well before the substance has run its course which can promote compulsive redosing, which can have extremely damaging cumulative effects.

Tactile hallucination - High doses and/or prolonged usage of certain stimulants like methamphetamine and cocaine can lead to hallucinatory sensations of bugs crawling on the surface of or underneath one’s skin. This is typically referred to as delusional parasitosis or more informally as “meth mites”.

Vibrating vision - At high doses or certain routes of administration, a person's eyeballs may begin to spontaneously wiggle back and forth in a rapid motion, causing the vision to become blurry and temporarily out of focus. This is a condition known as nystagmus.

Seizure - This is an uncommon effect but can happen in those predisposed to them, especially while in physically taxing conditions such as being dehydrated, fatigued or undernourished, or if miusing the substance for extended periods of time.

Visual effects

The visual effects of methamphetamine are usually less consistent and are only mildly noticeable at higher dosages. They are somewhat comparable to the visuals produced by deliriants and are more frequent in darker areas. Scenarios consisting of severe sleep deprivation caused by wakefulness can lead to more intense visual effects and even hallucinations.

Suppressions

Distortions

Visual drifting - This effect is usually subtle or barely noticeable and only occurs at higher dosages or when combined with cannabis. It is most prominent when smoked or taken intravenously and is usually delirious in nature. Commonly this, high dosages or prolonged use can cause level 1-2 visual drifting.

Hallucinatory states

Transformations - This effect occurs very rarely, and typically only when the user has taken high doses, is coming down, or has been awake for unusually long periods. They are usually very mild when they do happen to occur.

Cognitive effects

The cognitive effects of methamphetamine can be broken down into several components which progressively intensify proportional to dosage. The general head space of methamphetamine is described by many as one of extreme mental stimulation, increased focus, ego inflation and powerful euphoria. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate dosages, they become increasingly likely to manifest themselves with higher amounts or widespread usage. This particularly holds true during the offset of the experience.
The most prominent of these cognitive effects generally include:

After effects

The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:

Toxicity and harm potential

Unlike amphetamine, methamphetamine is directly neurotoxic to dopamine neurons.[17] Moreover, methamphetamine abuse is associated with an increased risk of Parkinson's disease due to excessive pre-synaptic dopamine autoxidation, a mechanism of neurotoxicity.[18][19][20][21] Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to serotoninneurons.[22] It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine.[23] As a result of methamphetamine-induced neurotoxicity to dopamine neurons, chronic use may also lead to post acute withdrawals which persist beyond the withdrawal period for months, and even up to a year.[24]

Lethal dosage

A methamphetamine overdose may result in a wide range of symptoms and is potentially fatal at heavy dosages.[25] A moderate overdose of methamphetamine may induce symptoms such as abnormal heart rhythm, confusion, dysuria, high or low blood pressure, hyperthermia, hyperreflexia, myalgia, severe agitation, tachypnea, tremor, urinary hesitancy, and urinary retention.[26] An extremely large overdose may produce symptoms such as adrenergic storm, methamphetamine psychosis, anuria, cardiogenic shock, cerebral hemorrhage, circulatory collapse, hyperpyrexia, pulmonary hypertension, renal failure, rhabdomyolysis, serotonin syndrome, and a form of stereotypy ("tweaking"). A methamphetamine overdose will likely also result in mild brain damage due to dopaminergic and serotonergic neurotoxicity.[27][28] Death from fatal methamphetamine poisoning is typically preceded by convulsions and coma.[29]

Tolerance and addiction potential

As with other stimulants, the chronic use of methamphetamine can be considered extremely addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

Tolerance to the effects of this compound rapidly develops with prolonged and repeated use.[30][31] This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Methamphetamine presents cross-tolerance with all dopaminergicstimulants, meaning that after the consumption of methamphetamine all stimulants will have a reduced effect.

The evidence on effective treatments for amphetamine and methamphetamine dependence and abuse is limited.[32] In light of this, fluoxetine and imipramine appear to have some limited benefits in treating abuse and addiction, "no treatment has been demonstrated to be effective for the treatment of methamphetamine dependence and abuse".[33]

In highly dependent amphetamine and methamphetamine abusers, "when chronic heavy users abruptly discontinue methamphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose".[34] Withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.[35] Methamphetamine withdrawal symptoms can include anxiety, drug craving, dysphoric mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and vivid or lucid dreams.[36] Withdrawal symptoms are associated with the degree of dependence (i.e., the extent of abuse).[37] The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal.[38]

Psychosis

Abuse of methamphetamine can result in a stimulant psychosis that may present with a variety of symptoms (e.g., paranoia, hallucinations, delusions).[39] A review on treatment for amphetamine, dextroamphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.[40][41] The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[42] Psychosis very rarely arises from therapeutic use.[43][44]

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.

Alcohol - Alcohol can be dangerous to combine with stimulants due to the risk of accidental over-intoxication. Stimulants mask the sedative effects of alcohol, which is the main factor people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects of alcohol are left unopposed, which can result in blackouts and respiratory depression. If combined, one should strictly limit themselves to only drinking a certain amount of alcohol per hour.

DXM - Combinations with DXM should be strictly avoided due to DXM's effects on serotonin and dopamine reuptake. This can lead to panic attacks, hypertensive crisis, or serotonin syndrome.

MXE - Combinations with MXE may dangerously elevate blood pressure and increase the risk of psychosis.

Tramadol - Tramadol lowers the seizure threshold.[46] Combinations with stimulants may further increase this risk.

Legality

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The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions.[48][49] Methamphetamine has been placed in Schedule II of the United Nations Convention on Psychotropic Substances treaty.[50]

Austria: Methamphetamine is illegal to possess, produce and sell under the SMG (Suchtmittelgesetz Österreich).[citation needed]

↑Rasmussen N (July 2006). "Making the first anti-depressant: amphetamine in American medicine, 1929–1950". J. Hist. Med. Allied Sci. 61 (3): 288–323. PMID 16492800. https://doi.org/0.1093/jhmas/jrj039. SKF first packaged it as an inhaler so as to exploit the base's volatility and, after sponsoring some trials by East Coast otolaryngological specialists, began to advertise the Benzedrine Inhaler as a decongestant in late 1933.

↑Rasmussen N (2011). "Medical science and the military: the Allies' use of amphetamine during World War II". J. Interdiscip. Hist. 42 (2): 205–233. PMID 22073434. https://doi.org/10.1162/JINH_a_00212